2021
Comparison of radiomic feature aggregation methods for patients with multiple tumors
Chang E, Joel MZ, Chang HY, Du J, Khanna O, Omuro A, Chiang V, Aneja S. Comparison of radiomic feature aggregation methods for patients with multiple tumors. Scientific Reports 2021, 11: 9758. PMID: 33963236, PMCID: PMC8105371, DOI: 10.1038/s41598-021-89114-6.Peer-Reviewed Original ResearchConceptsCox proportional hazards modelCox proportional hazardsProportional hazards modelBrain metastasesRadiomic featuresHazards modelProportional hazardsStandard Cox proportional hazards modelMultifocal brain metastasesMultiple brain metastasesNumber of patientsPatient-level outcomesHigher concordance indexRadiomic feature analysisRandom survival forest modelSurvival modelsDifferent tumor volumesMultifocal tumorsCancer outcomesMultiple tumorsMetastatic cancerConcordance indexTumor volumePatientsTumor types
2020
Genetic characterization of an aggressive optic nerve pilocytic glioma
Hong CS, Fliney G, Fisayo A, An Y, Gopal PP, Omuro A, Pointdujour-Lim R, Erson-Omay EZ, Omay SB. Genetic characterization of an aggressive optic nerve pilocytic glioma. Brain Tumor Pathology 2020, 38: 59-63. PMID: 33098465, PMCID: PMC7585354, DOI: 10.1007/s10014-020-00383-x.Peer-Reviewed Original ResearchConceptsOptic nerve gliomaLeft optic nerve sheathLeft-sided visual lossSporadic adult casesOptic nerve sheathNeurofibromatosis type 1 syndromeType 1 syndromeWhole-exome sequencingEmpiric managementVisual lossFocal radiotherapyOptic nervePediatric populationNerve sheathOpen biopsyAdult casesBiopsy specimenBenign histopathologyClinical prognosticationPilocytic astrocytomaComplex tumorsActionable targetsVisual pathwayAdult populationTumor progressionEffect of Nivolumab vs Bevacizumab in Patients With Recurrent Glioblastoma
Reardon DA, Brandes AA, Omuro A, Mulholland P, Lim M, Wick A, Baehring J, Ahluwalia MS, Roth P, Bähr O, Phuphanich S, Sepulveda JM, De Souza P, Sahebjam S, Carleton M, Tatsuoka K, Taitt C, Zwirtes R, Sampson J, Weller M. Effect of Nivolumab vs Bevacizumab in Patients With Recurrent Glioblastoma. JAMA Oncology 2020, 6: 1003-1010. PMID: 32437507, PMCID: PMC7243167, DOI: 10.1001/jamaoncol.2020.1024.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAngiogenesis InhibitorsAntineoplastic Agents, ImmunologicalBevacizumabBrain NeoplasmsDNA Modification MethylasesDNA Repair EnzymesFemaleGlioblastomaHumansImmune Checkpoint InhibitorsMaleMiddle AgedNeoplasm Recurrence, LocalNivolumabProgrammed Cell Death 1 ReceptorTemozolomideTreatment OutcomeTumor Suppressor ProteinsYoung AdultConceptsTreatment-related adverse eventsPhase 3 clinical trialsPrimary end pointOverall survivalRecurrent glioblastomaClinical trialsMedian OSGrade 3/4 treatment-related adverse eventsRandomized phase 3 clinical trialSingle-agent PD-1 blockadeEnd pointEffects of nivolumabUnacceptable toxic effectsMedian overall survivalObjective response ratePD-1 blockadeOverall patient populationImmune checkpoint blockadeData cutoffAdverse eventsCheckpoint blockadeFirst recurrenceInhibitor therapyClinical outcomesSafety profileCerebrospinal fluid circulating tumor cells as a quantifiable measurement of leptomeningeal metastases in patients with HER2 positive cancer
Malani R, Fleisher M, Kumthekar P, Lin X, Omuro A, Groves MD, Lin NU, Melisko M, Lassman AB, Jeyapalan S, Seidman A, Skakodub A, Boire A, DeAngelis LM, Rosenblum M, Raizer J, Pentsova E. Cerebrospinal fluid circulating tumor cells as a quantifiable measurement of leptomeningeal metastases in patients with HER2 positive cancer. Journal Of Neuro-Oncology 2020, 148: 599-606. PMID: 32506369, PMCID: PMC7438284, DOI: 10.1007/s11060-020-03555-z.Peer-Reviewed Original ResearchConceptsLeptomeningeal metastasesCSF cytologyCSF CTCsCTC enumerationCerebrospinal fluidIT trastuzumabPhase I/II dose escalation trialCentral nervous system compartmentTumor cellsHER2/neu positivityHER2/neu expressionDose-escalation trialHER2-positive cancersIntrathecal trastuzumabEscalation trialRadiographic responseTumor burdenPositive cancersNeu expressionNeu positivityConclusionOur studyPatientsDay 1Epithelial cancersCancerPhase I clinical trial of temsirolimus and perifosine for recurrent glioblastoma
Kaley TJ, Panageas KS, Pentsova EI, Mellinghoff IK, Nolan C, Gavrilovic I, DeAngelis LM, Abrey LE, Holland EC, Omuro A, Lacouture ME, Ludwig E, Lassman AB. Phase I clinical trial of temsirolimus and perifosine for recurrent glioblastoma. Annals Of Clinical And Translational Neurology 2020, 7: 429-436. PMID: 32293798, PMCID: PMC7187704, DOI: 10.1002/acn3.51009.Peer-Reviewed Original ResearchConceptsRecurrent malignant gliomaDose-limiting toxicityMTOR inhibitor temsirolimusMalignant gliomasAkt inhibitor perifosinePhase I clinical trialDose level 3Dose level 7Phase II doseSynergistic anti-tumor effectKarnofsky performance statusPhase I trialDeadly primary brain cancerPI3K/Akt/mTOR axisPrimary brain cancerAkt/mTOR axisAnti-tumor effectsPotential therapeutic targetMost malignant gliomasPrior therapyTemsirolimus dosePerformance statusI trialIntracerebral hemorrhageCombined therapy
2019
Longitudinal cognitive assessment in patients with primary CNS lymphoma treated with induction chemotherapy followed by reduced-dose whole-brain radiotherapy or autologous stem cell transplantation
Correa DD, Braun E, Kryza-Lacombe M, Ho KW, Reiner AS, Panageas KS, Yahalom J, Sauter CS, Abrey LE, DeAngelis LM, Omuro A. Longitudinal cognitive assessment in patients with primary CNS lymphoma treated with induction chemotherapy followed by reduced-dose whole-brain radiotherapy or autologous stem cell transplantation. Journal Of Neuro-Oncology 2019, 144: 553-562. PMID: 31377920, PMCID: PMC7392129, DOI: 10.1007/s11060-019-03257-1.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Combined Chemotherapy ProtocolsCentral Nervous System NeoplasmsCognitionCombined Modality TherapyCranial IrradiationFemaleFollow-Up StudiesHematopoietic Stem Cell TransplantationHumansInduction ChemotherapyLongitudinal StudiesLymphomaMaleMiddle AgedPrognosisQuality of LifeSurvival RateTransplantation, AutologousYoung AdultConceptsWhole brain radiotherapyReduced-dose whole-brain radiotherapyPrimary central nervous system lymphomaHDC-ASCTCortical atrophyAttention/executive functionPCNSL patientsAutologous stem cell transplantConsolidation whole-brain radiotherapyAutologous stem cell transplantationCentral nervous system lymphomaCognitive functionIntroductionThe standard treatmentLongitudinal cognitive assessmentsProgression-free patientsHigh-dose chemotherapyMethotrexate-based chemotherapyLong-term remissionPrimary CNS lymphomaNervous system lymphomaStem cell transplantStem cell transplantationBrain structure abnormalitiesPost-induction chemotherapyWhite matter diseaseSequencing and curation strategies for identifying candidate glioblastoma treatments
Frank MO, Koyama T, Rhrissorrakrai K, Robine N, Utro F, Emde AK, Chen BJ, Arora K, Shah M, Geiger H, Felice V, Dikoglu E, Rahman S, Fang A, Vacic V, Bergmann EA, Vogel JLM, Reeves C, Khaira D, Calabro A, Kim D, Lamendola-Essel MF, Esteves C, Agius P, Stolte C, Boockvar J, Demopoulos A, Placantonakis DG, Golfinos JG, Brennan C, Bruce J, Lassman AB, Canoll P, Grommes C, Daras M, Diamond E, Omuro A, Pentsova E, Orange DE, Harvey SJ, Posner JB, Michelini VV, Jobanputra V, Zody MC, Kelly J, Parida L, Wrzeszczynski KO, Royyuru AK, Darnell RB. Sequencing and curation strategies for identifying candidate glioblastoma treatments. BMC Medical Genomics 2019, 12: 56. PMID: 31023376, PMCID: PMC6485090, DOI: 10.1186/s12920-019-0500-0.Peer-Reviewed Original ResearchConceptsPotential treatment optionClinical research studiesWhole-genome sequencingPharmacologic interventionsCancer patientsTreatment optionsClinical resultsPatientsConclusionThese resultsGlioblastoma treatmentPotential cancer treatmentPanel sequencingActionable variantsCancer treatmentGlioblastoma tumorsSame variantSequencing assaysDrug targetsRNA sequencingRNA-seqTreatmentNew York CitySequencingTumorsCliniciansResidual Tumor Volume, Cell Volume Fraction, and Tumor Cell Kill During Fractionated Chemoradiation Therapy of Human Glioblastoma using Quantitative Sodium MR Imaging
Thulborn KR, Lu A, Atkinson IC, Pauliah M, Beal K, Chan TA, Omuro A, Yamada J, Bradbury MS. Residual Tumor Volume, Cell Volume Fraction, and Tumor Cell Kill During Fractionated Chemoradiation Therapy of Human Glioblastoma using Quantitative Sodium MR Imaging. Clinical Cancer Research 2019, 25: 1226-1232. PMID: 30487127, PMCID: PMC7462306, DOI: 10.1158/1078-0432.ccr-18-2079.Peer-Reviewed Original ResearchConceptsResidual tumor volumeTumor cell killTissue sodium concentrationChemoradiation therapyOverall survivalHuman glioblastomaTumor volumeQuantitative sodium MR imagingCell killQuantitative sodium MRITumor cellsVariable tumor responseSodium MRITwo-compartment modelTumor resectionTumor responseDisease progressionSodium MR imagingTumor marginsMR imagingTherapyGlioblastomaTreatment volumeCancer cellsSodium concentrationBuparlisib in Patients With Recurrent Glioblastoma Harboring Phosphatidylinositol 3-Kinase Pathway Activation: An Open-Label, Multicenter, Multi-Arm, Phase II Trial
Wen PY, Touat M, Alexander BM, Mellinghoff IK, Ramkissoon S, McCluskey CS, Pelton K, Haidar S, Basu SS, Gaffey SC, Brown LE, Martinez-Ledesma JE, Wu S, Kim J, Wei W, Park MA, Huse JT, Kuhn JG, Rinne ML, Colman H, Agar NYR, Omuro AM, DeAngelis LM, Gilbert MR, de Groot JF, Cloughesy TF, S. A, Roberts TM, Zhao JJ, Lee EQ, Nayak L, Heath JR, Horky LL, Batchelor TT, Beroukhim R, Chang SM, Ligon AH, Dunn IF, Koul D, Young GS, Prados MD, Reardon DA, Yung WKA, Ligon KL. Buparlisib in Patients With Recurrent Glioblastoma Harboring Phosphatidylinositol 3-Kinase Pathway Activation: An Open-Label, Multicenter, Multi-Arm, Phase II Trial. Journal Of Clinical Oncology 2019, 37: jco.18.01207. PMID: 30715997, PMCID: PMC6553812, DOI: 10.1200/jco.18.01207.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAminopyridinesAntineoplastic AgentsBrain NeoplasmsChemotherapy, AdjuvantDisease ProgressionEnzyme ActivationFemaleGlioblastomaHumansMaleMiddle AgedMorpholinesNeoadjuvant TherapyNeoplasm Recurrence, LocalPhosphatidylinositol 3-KinasePhosphoinositide-3 Kinase InhibitorsProgression-Free SurvivalTime FactorsConceptsPhase II trialCohort 2Cohort 1PI3K pathwayTumor tissueII trialRecurrent glioblastomaBrain penetrationPan-PI3K inhibitor buparlisibPathway inhibitionPathway activationCommon grade 3K pathwayPrimary end pointGreater adverse eventsProgression-free survivalPI3K pathway inhibitionPI3K pathway activationPlasma drug levelsSingle-agent efficacySignificant brain penetrationPI3K inhibitorsMedian PFSOpen labelAdverse events
2018
Phase 1 study of pomalidomide and dexamethasone for relapsed/refractory primary CNS or vitreoretinal lymphoma
Tun HW, Johnston PB, DeAngelis LM, Atherton PJ, Pederson LD, Koenig PA, Reeder CB, Omuro AMP, Schiff D, O'Neill B, Pulido J, Jaeckle KA, Grommes C, Witzig TE. Phase 1 study of pomalidomide and dexamethasone for relapsed/refractory primary CNS or vitreoretinal lymphoma. Blood 2018, 132: 2240-2248. PMID: 30262659, PMCID: PMC6265643, DOI: 10.1182/blood-2018-02-835496.Peer-Reviewed Original ResearchConceptsPrimary central nervous system lymphomaOverall response ratePrimary vitreoretinal lymphomaProgression-free survivalRefractory primary central nervous system lymphomaComplete responsePartial responseVitreoretinal lymphomaGrade 3/4 hematologic toxicitiesGrade 3/4 nonhematologic toxicitiesMedian progression-free survivalCentral nervous system lymphomaDose escalation schedulePhase 1 studyNervous system lymphomaCombination of pomalidomideSignificant therapeutic activityMTD cohortNonhematologic toxicityHematologic toxicityRespiratory failureSystem lymphomaMTD determinationPrimary CNSSafety profileMulticenter Phase IB Trial of Carboxyamidotriazole Orotate and Temozolomide for Recurrent and Newly Diagnosed Glioblastoma and Other Anaplastic Gliomas.
Omuro A, Beal K, McNeill K, Young RJ, Thomas A, Lin X, Terziev R, Kaley TJ, DeAngelis LM, Daras M, Gavrilovic IT, Mellinghoff I, Diamond EL, McKeown A, Manne M, Caterfino A, Patel K, Bavisotto L, Gorman G, Lamson M, Gutin P, Tabar V, Chakravarty D, Chan TA, Brennan CW, Garrett-Mayer E, Karmali RA, Pentsova E. Multicenter Phase IB Trial of Carboxyamidotriazole Orotate and Temozolomide for Recurrent and Newly Diagnosed Glioblastoma and Other Anaplastic Gliomas. Journal Of Clinical Oncology 2018, 36: 1702-1709. PMID: 29683790, PMCID: PMC5993168, DOI: 10.1200/jco.2017.76.9992.Peer-Reviewed Original ResearchConceptsAnaplastic gliomasCohort 2Cohort 1Median progression-free survivalFavorable brain penetrationMedian overall survivalPhase Ib studyPhase Ib trialPhase II doseProgression-free survivalRecurrent anaplastic gliomasDependent calcium channelsNovel oral inhibitorSignal of activityMismatch repair genesIb trialTreat populationMethylguanine-DNA methyltransferaseOverall survivalComplete responseFlat doseOral inhibitorBrain penetrationResults FortyTherapeutic concentrationsIn Vivo PET Assay of Tumor Glutamine Flux and Metabolism: In-Human Trial of 18F-(2S,4R)-4-Fluoroglutamine.
Dunphy MPS, Harding JJ, Venneti S, Zhang H, Burnazi EM, Bromberg J, Omuro AM, Hsieh JJ, Mellinghoff IK, Staton K, Pressl C, Beattie BJ, Zanzonico PB, Gerecitano JF, Kelsen DP, Weber W, Lyashchenko SK, Kung HF, Lewis JS. In Vivo PET Assay of Tumor Glutamine Flux and Metabolism: In-Human Trial of 18F-(2S,4R)-4-Fluoroglutamine. Radiology 2018, 287: 667-675. PMID: 29388903, PMCID: PMC5929369, DOI: 10.1148/radiol.2017162610.Peer-Reviewed Original ResearchConceptsPositron emission tomographyDifferent cancer typesCancer typesAcid levelsFisher's exact testAmino acid levelsInvestigational new drug applicationGlutamine metabolismInstitutional review boardFluorodeoxyglucose avidityAdult patientsIntravenous bolusAcute fastingAggressive tumorsClinical safetyPotential tumor biomarkerPET scansPatientsExact testHelsinki DeclarationDrug AdministrationNew drug applicationsEmission tomographyTumorsInformed consentRadiographic patterns of recurrence and pathologic correlation in malignant gliomas treated with bevacizumab
Thomas A, Rosenblum M, Karimi S, DeAngelis LM, Omuro A, Kaley TJ. Radiographic patterns of recurrence and pathologic correlation in malignant gliomas treated with bevacizumab. CNS Oncology 2018, 07: 7-13. PMID: 29388793, PMCID: PMC6001559, DOI: 10.2217/cns-2017-0025.Peer-Reviewed Original ResearchConceptsMalignant gliomasRecurrence patternsDiffusion-weighted imaging abnormalitiesDiffusion-weighted imagingStandard clinical settingMG patientsImaging abnormalitiesMRI abnormalitiesPathologic findingsTumor recurrenceRadiographic patternsPathologic correlationBevacizumabClinical settingNecrosisPatientsRecurrenceRecent reportsTumorsGliomasAbnormalitiesLeptomeningealSurgery
2017
Overall survival in patients with glioblastoma before and after bevacizumab approval
Johnson DR, Omuro AMP, Ravelo A, Sommer N, Guerin A, Ionescu-Ittu R, Shi S, Macalalad A, Uhm JH. Overall survival in patients with glioblastoma before and after bevacizumab approval. Current Medical Research And Opinion 2017, 34: 813-820. PMID: 29025274, DOI: 10.1080/03007995.2017.1392294.Peer-Reviewed Original ResearchConceptsOverall survivalTreatment of patientsBevacizumab approvalProgressive glioblastomaGBM diagnosisUS population-based cancer registry dataPopulation-based cancer registry dataCox proportional hazards regressionLarge population-based studyOS of patientsApproval of bevacizumabGross total resectionKaplan-Meier analysisPopulation-based studyProportional hazards regressionLimited therapeutic optionsCancer registry dataAdjusted hazardAdult patientsMedian ageTotal resectionStudy cohortAggressive diseaseHazards regressionTherapeutic optionsNivolumab with or without ipilimumab in patients with recurrent glioblastoma: results from exploratory phase I cohorts of CheckMate 143
Omuro A, Vlahovic G, Lim M, Sahebjam S, Baehring J, Cloughesy T, Voloschin A, Ramkissoon SH, Ligon KL, Latek R, Zwirtes R, Strauss L, Paliwal P, Harbison CT, Reardon DA, Sampson JH. Nivolumab with or without ipilimumab in patients with recurrent glioblastoma: results from exploratory phase I cohorts of CheckMate 143. Neuro-Oncology 2017, 20: 674-686. PMID: 29106665, PMCID: PMC5892140, DOI: 10.1093/neuonc/nox208.Peer-Reviewed Original ResearchConceptsAdverse eventsRecurrent glioblastomaCommon treatment-related adverse eventsTreatment-related adverse eventsDeath ligand 1 (PD-L1) expressionEffects of nivolumabExploratory efficacy outcomesSafety/tolerabilityFindings merit further investigationLigand 1 expressionCheckMate 143Ipilimumab doseNivolumab monotherapyStable diseaseAlternative regimenEfficacy outcomesRadiographic progressionMost patientsPartial responseNivolumabIpilimumabMerit further investigationPatientsI cohortFurther evaluationIbrutinib Unmasks Critical Role of Bruton Tyrosine Kinase in Primary CNS Lymphoma
Grommes C, Pastore A, Palaskas N, Tang SS, Campos C, Schartz D, Codega P, Nichol D, Clark O, Hsieh WY, Rohle D, Rosenblum M, Viale A, Tabar VS, Brennan CW, Gavrilovic IT, Kaley TJ, Nolan CP, Omuro A, Pentsova E, Thomas AA, Tsyvkin E, Noy A, Palomba ML, Hamlin P, Sauter CS, Moskowitz CH, Wolfe J, Dogan A, Won M, Glass J, Peak S, Lallana EC, Hatzoglou V, Reiner AS, Gutin PH, Huse JT, Panageas KS, Graeber TG, Schultz N, DeAngelis LM, Mellinghoff IK. Ibrutinib Unmasks Critical Role of Bruton Tyrosine Kinase in Primary CNS Lymphoma. Cancer Discovery 2017, 7: 1018-1029. PMID: 28619981, PMCID: PMC5581705, DOI: 10.1158/2159-8290.cd-17-0613.Peer-Reviewed Original ResearchMeSH KeywordsAdenineAdultAgammaglobulinaemia Tyrosine KinaseAgedAged, 80 and overAntineoplastic AgentsCARD Signaling Adaptor ProteinsCentral Nervous System NeoplasmsDrug Resistance, NeoplasmFemaleGuanylate CyclaseHumansLymphoma, B-CellMaleMaximum Tolerated DoseMiddle AgedMutationPiperidinesProtein Kinase InhibitorsProtein-Tyrosine KinasesPyrazolesPyrimidinesTreatment OutcomeYoung AdultConceptsPrimary central nervous system lymphomaBruton's tyrosine kinaseB-cell lymphomaRefractory B-cell lymphomaB cell antigen receptorCentral nervous system lymphomaRole of BTKDiffuse large B-cell lymphomaLarge B-cell lymphomaPhase I clinical trialClass BTK inhibitorIncomplete tumor responseNervous system lymphomaToll-like receptorsPI3K/mTORIbrutinib responseCNS lymphomaClinical responseComplete responseReceptor-associated proteinSystem lymphomaActivation markersTumor responseClinical trialsPCNSL cellsMulticenter, Phase 1, Dose Escalation Study of Hypofractionated Stereotactic Radiation Therapy With Bevacizumab for Recurrent Glioblastoma and Anaplastic Astrocytoma
Clarke J, Neil E, Terziev R, Gutin P, Barani I, Kaley T, Lassman AB, Chan TA, Yamada J, DeAngelis L, Ballangrud A, Young R, Panageas KS, Beal K, Omuro A. Multicenter, Phase 1, Dose Escalation Study of Hypofractionated Stereotactic Radiation Therapy With Bevacizumab for Recurrent Glioblastoma and Anaplastic Astrocytoma. International Journal Of Radiation Oncology • Biology • Physics 2017, 99: 797-804. PMID: 28870792, PMCID: PMC5654655, DOI: 10.1016/j.ijrobp.2017.06.2466.Peer-Reviewed Original ResearchMeSH KeywordsAgedAngiogenesis InhibitorsAstrocytomaBevacizumabBrainBrain NeoplasmsFemaleGlioblastomaHumansIntention to Treat AnalysisKarnofsky Performance StatusMaleMaximum Tolerated DoseMiddle AgedNeoplasm Recurrence, LocalOrgans at RiskProspective StudiesRadiation Dose HypofractionationRadiosurgeryRe-IrradiationTumor BurdenConceptsRecurrent high-grade gliomaDose-limiting toxicityHigh-grade gliomasStereotactic reirradiationHypofractionated Stereotactic Radiation TherapyCorpus callosum involvementDose level cohortsGrade 3 fatigueMedian overall survivalKarnofsky performance statusDose-escalation studyTreatment-related effectsBiological equivalent doseStereotactic radiation therapyWarrants further investigationAbsence of brainstemDose-escalation trial designBevacizumab dosesCallosum involvementConcomitant bevacizumabSymptomatic radionecrosisEscalation studyOverall survivalPerformance statusResected specimensCerebrospinal fluid circulating tumor cells: a novel tool to diagnose leptomeningeal metastases from epithelial tumors
Lin X, Fleisher M, Rosenblum M, Lin O, Boire A, Briggs S, Bensman Y, Hurtado B, Shagabayeva L, DeAngelis LM, Panageas KS, Omuro A, Pentsova EI. Cerebrospinal fluid circulating tumor cells: a novel tool to diagnose leptomeningeal metastases from epithelial tumors. Neuro-Oncology 2017, 19: 1248-1254. PMID: 28821205, PMCID: PMC5570249, DOI: 10.1093/neuonc/nox066.Peer-Reviewed Original ResearchConceptsDiagnosis of LMLeptomeningeal metastasesCSF CTCsCSF cytologyEpithelial tumorsMRI findingsOptimal cutoffInstitutional review board-approved prospective studyTumor cellsNegative predictive value 97ROC analysisRare cell capture technologyPositive predictive value 90Positive CSF cytologyCSF of patientsSolid tumor patientsPrevious pilot studyClinical suspicionProspective studyCytology examinationTumor patientsLarge cohortCerebrospinal fluidPatientsStandard MRIMutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients
Zehir A, Benayed R, Shah RH, Syed A, Middha S, Kim HR, Srinivasan P, Gao J, Chakravarty D, Devlin SM, Hellmann MD, Barron DA, Schram AM, Hameed M, Dogan S, Ross DS, Hechtman JF, DeLair DF, Yao J, Mandelker DL, Cheng DT, Chandramohan R, Mohanty AS, Ptashkin RN, Jayakumaran G, Prasad M, Syed MH, Rema AB, Liu ZY, Nafa K, Borsu L, Sadowska J, Casanova J, Bacares R, Kiecka IJ, Razumova A, Son JB, Stewart L, Baldi T, Mullaney KA, Al-Ahmadie H, Vakiani E, Abeshouse AA, Penson AV, Jonsson P, Camacho N, Chang MT, Won HH, Gross BE, Kundra R, Heins ZJ, Chen HW, Phillips S, Zhang H, Wang J, Ochoa A, Wills J, Eubank M, Thomas SB, Gardos SM, Reales DN, Galle J, Durany R, Cambria R, Abida W, Cercek A, Feldman DR, Gounder MM, Hakimi AA, Harding JJ, Iyer G, Janjigian YY, Jordan EJ, Kelly CM, Lowery MA, Morris LGT, Omuro AM, Raj N, Razavi P, Shoushtari AN, Shukla N, Soumerai TE, Varghese AM, Yaeger R, Coleman J, Bochner B, Riely GJ, Saltz LB, Scher HI, Sabbatini PJ, Robson ME, Klimstra DS, Taylor BS, Baselga J, Schultz N, Hyman DM, Arcila ME, Solit DB, Ladanyi M, Berger MF. Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients. Nature Medicine 2017, 23: 703-713. PMID: 28481359, PMCID: PMC5461196, DOI: 10.1038/nm.4333.Peer-Reviewed Original ResearchConceptsMemorial Sloan-Kettering Cancer CenterCancer-related genesProspective clinical sequencingAdvanced solid cancersSequencing platformsStructural variantsGenomic landscapeGenomic mutationsDetailed clinical annotationMutational landscapeSequencing resultsNumber alterationsCancer CenterPatient enrollmentClinical trialsMSK-IMPACTMetastatic cancerSolid cancersNew insightsNormal tissuesClinical sequencingCancer therapyPatientsCancerClinical annotationMulticenter phase II study of temozolomide and myeloablative chemotherapy with autologous stem cell transplant for newly diagnosed anaplastic oligodendroglioma
Thomas AA, Abrey LE, Terziev R, Raizer J, Martinez NL, Forsyth P, Paleologos N, Matasar M, Sauter CS, Moskowitz C, Nimer SD, DeAngelis LM, Kaley T, Grimm S, Louis DN, Cairncross JG, Panageas KS, Briggs S, Faivre G, Mohile NA, Mehta J, Jonsson P, Chakravarty D, Gao J, Schultz N, Brennan CW, Huse JT, Omuro A. Multicenter phase II study of temozolomide and myeloablative chemotherapy with autologous stem cell transplant for newly diagnosed anaplastic oligodendroglioma. Neuro-Oncology 2017, 19: 1380-1390. PMID: 28472509, PMCID: PMC5596171, DOI: 10.1093/neuonc/nox086.Peer-Reviewed Original ResearchConceptsAutologous stem cell transplantProgression-free survivalHigh-dose chemotherapyStem cell transplantAnaplastic oligodendrogliomaAnaplastic oligoastrocytomaHDC-ASCTMulticenter phase II studyMyeloablative high-dose chemotherapyChemotherapy-based approachesCycles of temozolomideOverall survival 93Phase II studyRadiation-related toxicityUnexpected adverse eventsNext-generation sequencingChemotherapy-sensitive tumorsWide molecular heterogeneityToxic deathsAdverse eventsII studyMyeloablative chemotherapyProspective trialIntact patientsCell transplant